Base and Nucleophile

[deuteronomy31.8]

Hey guys need a help with orgo where I can't get my mind of this concept.

So I bumped into this dilemma where I see a base that deprotonate an alpha hydrogen
and sometimes I see a base that attack the carbonyl carbon as a nucleophile.
What would be a good standard to be able to distinguish these two type of bases?

For example, a grignard, as a base, would love to take the hydrogen away.
However, I see multiple reactions where the grignard attacks as a nucleophile.

I feel like I'm missing some strong concept here.

---

Members don't see this ad.

 

[DAT Destroyer]

You have asked a very sophisticated question which I often discuss in my Advanced Organic Chemistry class. The answer involves orbital concepts from BOTH Physical-Organic Chemistry and Quantum Chemistry, but I will spell it out in easy to understand English. Let us consider a ketone. A nucleophile can attack the carbonyl or it can remove an alpha hydrogen as you so perspicaciously have noted. A Grignard will almost always attack the carbonyl group as would alkyl lithium reagents and hydride anions from reagents such as NaBH4 or LiAlH4. These reagents are more sensitive to charge development in the transition state, hence attack the carbonyl. Other nucleophiles such as Methoxide, Ethoxide, and sterically hindered O and N containing bases such as LDA will abstract an alpha hydrogen since orbital control DOMINATES charge control. Grignard does poorly removing an alpha hydrogen as does the alkyl lithium reagents when a carbonyl is available. For the DAT or OAT exam.....it will be a VERY safe bet to always attack the carbonyl with Grignard or Alkyl Lithium reagents and reducing agents like hydrides,,,,,,,and for O or N containing bases , abstract an alpha hydrogen. Hope this helps.

Dr. Romano, co/owner/DAT Destroyer/Orgoman

 

[deleted982220]

Acid/base reactions occur faster than nucleophile/electrophile reactions. Grignards/ organometallics will react with an acidic proton before doing a nucleophile/electrophile reaction. Water, alcohols, carboxylic acids, and others that have acidic protons will kill the Grignard/organometallic(s). Check to make sure you don't have acidic protons, such as an alpha hydrogen (know how to recognize these). Strong concept you're missing here: Acid/base reactions occur faster than nucleophile/electrophile reactions.

 

[deuteronomy31.8]

You have asked a very sophisticated question which I often discuss in my Advanced Organic Chemistry class. The answer involves orbital concepts from BOTH Physical-Organic Chemistry and Quantum Chemistry, but I will spell it out in easy to understand English. Let us consider a ketone. A nucleophile can attack the carbonyl or it can remove an alpha hydrogen as you so perspicaciously have noted. A Grignard will almost always attack the carbonyl group as would alkyl lithium reagents and hydride anions from reagents such as NaBH4 or LiAlH4. These reagents are more sensitive to charge development in the transition state, hence attack the carbonyl. Other nucleophiles such as Methoxide, Ethoxide, and sterically hindered O and N containing bases such as LDA will abstract an alpha hydrogen since orbital control DOMINATES charge control. Grignard does poorly removing an alpha hydrogen as does the alkyl lithium reagents when a carbonyl is available. For the DAT or OAT exam.....it will be a VERY safe bet to always attack the carbonyl with Grignard or Alkyl Lithium reagents and reducing agents like hydrides,,,,,,,and for O or N containing bases , abstract an alpha hydrogen. Hope this helps.

Dr. Romano, co/owner/DAT Destroyer/Orgoman

Thank you so much Dr. Romano !
it couldn't be any clearer than the explanation you provided.

by the way, I actually came up with this problem while going through the Destroyer.
It has been a tremendous help so far and I appreciate it again!

 

[deuteronomy31.8]

Acid/base reactions occur faster than nucleophile/electrophile reactions. Grignards/ organometallics will react with an acidic proton before doing a nucleophile/electrophile reaction. Water, alcohols, carboxylic acids, and others that have acidic protons will kill the Grignard/organometallic(s). Check to make sure you don't have acidic protons, such as an alpha hydrogen (know how to recognize these). Strong concept you're missing here: Acid/base reactions occur faster than nucleophile/electrophile reactions.

Wow, can't believe I missed that while going over the concepts.
Thanks for opening up a new orgo insight for me